17alpha-(aliphatic hydrocarbon)-4, 5-epoxy-19-norandrostane-3beta, 17beta-diols and lower alkanoates thereof



pounds.

United States Patent 17a-(ALIPHATIC HYDROCARBON) 4,5 EPOXY-19- NORANDROSTANE 3,8,1713 DIOLS AND LOWER ALKANOATES THEREOF Paul D. Klimstra, Northbrook, Ill., assignor to G. D. Searle & Co., Chicago, III., a corporation of Delaware N0 Drawing. Filed July 25, 1963, Ser. No. 297,683

15 Claims. (Cl. 260-23955) This invention is concerned with 4,5-epoxy-19-norsteroids and, more particularly, with Hot-(aliphatic hydrocarbon) -4,5 -epoxy-19-norandrostane-3 B, 17 fi-diols and the corresponding lower alkanoyl esters. The compounds specifically contemplated can be represented by the structural formula wherein X represents a lower aliphatic hydrocarbon radical, R and R can be hydrogen or a lower alkanoyl radical, and the wavy lines are indicative of the alternative a and B configurations of the 4,5-epoxy group.

The lower aliphatic hydrocarbon radicals designated by X in the foregoing representation are exemplified by methyl, ethyl, isopropyl, secondary-butyl, tertiary-butyl, pentyl, hexyl, heptyl, vinyl, propenyl, allyl, crotyl, butenyl, pentenyl, hexenyl, heptenyl, ethynyl, propynyl, propargyl, butynyl, pentynyl, hexynyl, and heptynyl, i.e., those groups containing less than 8 carbon atoms. The lower alkanoyl radicals symbolized by R and R include acetyl, propionyl, butyryl, valeryl, caproyl, heptanoyl, and the corresponding branched-chain groups isomeric therewith.

The compounds of the present invention can be manufactured by epoxidation of the corresponding 17a-(lower aliphatic hydrocarbon)-l9-norandrost-4-ene-3B,l7B-diols and the corresponding lower alkanoate esters represented by the structural formula peracetic acid, and monoperphthalic acid. An inert nonpolar organic solvent such as carbon tetrachloride, benzene, or toluene is the preferred reaction medium, and the process may be carried out conveniently at or near room temperature. When the starting material contains a 3-hydroxy group, the instant 4,8,5B-epoxy derivatives are I produced while utilization of the 3-(lower alkanoyl)oxy starting materials results in the instant 4u,5a-epoxy com- Specific illustrations of the process in question are the reaction of 17u-ethynyl-19-norandrost-4-ene-3p8, 17B-diol and 17a-ethynyl-19-norandrost 4 ene 35,1758- diol 3,17-diacetate with a benzene solution of perbenzoic acid to aiford 4,B,5,8-epoxy-17u-ethynyl-19-norandrostane- 3,8,17,6-diol and 4u,5a-epoxy-17a-ethynyl 19 -norandrostane3,l3,17fi-diol 3,17-diacetate, respectively.

Partial catalytic hydrogenation of the instant 17a- (lower alkynyl) compounds provides an alternate method for the preparation of the Not-(lower alkenyl) substances of the present invention. As a specific example, the aforementioned 4B,5fl-e poxy-17a-ethynyl 19 norandrostane-3fi,17fi-diol in pyridine is shaken with 5% palladiumon-carbon catalysts to yield 45,5/3-epoxy-17a-vinyl-19- norandrostane-3,8,17B-diol.

Complete saturation of the acetylenic linkage of the aforementioned 17u-(lower alkynyl) derivatives by catalytic reduction results in the instant 17w-(lower alkyl) substances wherein the alkyl group contains more than one carbon atom. Typically, the hydrogenation of 40a,- Szx-epoxy-l7a-ethynyl-19-norandrostane-3B,17/3-diol 3,17-

diacetate in ethanol with a suitable catalyst such as 5% palladium-on-carbon results in 4a,5a-epoxy-17a-ethyl-19- norandrostane-3B,l7fi-diol 3,17-diacetate.

The 3-hydroxy-4zx,5a-epoxy compounds encompassed by the present invention are conveniently obtained by hydrolysis of the corresponding 3-(lower alkanoates). Thus, alkaline saponification of 4u,5u-epoxy17a-ethynyll9-norandrostane-3 8,175 diol 3,17 diacetate or 4:,5otepoxy-l7u-ethynyl-19-norandrostane-3fi,17,6 diol 3 acetate yields 4a,5u-'epoxy-l7a-ethynyl 19 norandrostane- 3,6,17 3-diol 17-acetate and 4a.,5e-epoxy-17a-ethynyl-19- norandrostane-3B,17B-diol, respectively.

Esterification of the instant 4,8,5B-epoxy 3 hydroxy compounds with a suitable acylating agent such as a lower alkanoic acid anhydride or halide in the presence of a suitable alkaline catalyst such as pyridine or triethylamine affords the corresponding 45,5,8-epoxy- 3 (lower alkanoyl)oxy derivatives. The reaction of 4,6,5/3-epoxy-l7aethynyl-l9-norandrostane-35,175 diol or 43,5,8 epoxyl7a-ethynyl-l9-norandrostane-3fi,17/3-diol l7-acetate, for example, with acetic anhydride in pyridine affords 413,55- epoxy-17u-ethynyl-l9-norandrostane-3fi,17fl-diol 3-acetate and 45,5[3-epoxy-17e-ethynyl-19-norandrostane 313,176- diol 3,17-diacetate, respectively.

The compounds of this invention are characterized by valuable pharmacological properties. They possess hormonal activity, for example, as is exemplified by their ability to evoke a uterine deciduogenic response. In addition, they display androgenic, anabolic, and anti-estrogenic activity.

The following examples illustrate in further detail some of the compounds which constitute this invention and methods for their preparation. However, this invention is not to be construed as limited thereby either in spirit or in scope as numerous modifications in materials and methods can be adopted without departing from the invenn'on herein described. In these examples, temperatures are indicated in degrees centigrade C.) and quantities of materials in parts by weight unless otherwise noted.

Example 1 To a mixture of 3.4 parts of lithium aluminum hydride and 111 parts of tetrahydrofuran, in a nitrogen atmosphere, is added, with stirring and cooling by means of an ice bath, a solution of 20 parts of tertiary-butyl alcohol in 22 parts of tetrahydrofuran over a period of about 45 minutes. To the resulting mixture is then added a solution of 10 parts of 175-acetoxy-17a-ethynyl-l9-norandrost-4-en-3-one in 133 parts of tetrahydrofuran. This reaction mixture is stirred at room temperature for about 3 hours, then is poured into 3600 parts of a mixture of ice and water containing parts of acetic acid. The precipitate which forms is collected by filtration, washed successively on the filter with water, 5% aqueous sodium bicarbonate, and water, then is dried in air. The result- Patented Mar. 36, 1365 .3,17-diacetate, melting at about 172175.

. ing crude product is recrystallized from aqueous methanol to yield 17a-ethynyl-19-norandrost-4-cne6p,17/3-diol 17- aeetate, which melts at about 18l182.5

Example 2 Example 3 A mixture of 30 parts of 17e-ethynyl-19-norandrost-4- ene3fi,17[5'-diol, 360 parts of dry pyridine, and 111 parts of acetic anhydride, under nitrogen, is stirred and heated at the reflux temperature for about 5 hours. This reaction mixture is cooled, then poured into approximately 3500 parts of cold water, and the resulting aqueous mixture is stirred at room temperature for about /2 hour. The precipitate which forms is collected by filtration, then is washed on the filter with Water and dried in air. This solid material is extracted into ether, and the ether solution is washed successively with aqueous hydrochloric acid and 5% aqueus sodium bicarbonate. Drying over anhydrous sodium sulfate containing decolorizing carbon followed by removal of the solvent by distillation at reduced pressure affords an oil which solidifies on standing. Recrystallization of that solid by dropwise dilution with water of a methanol solution affords 170:.- ethynyl-19-norandrost-4-ene-3B,17B diol 3,17 diacetate, melting at about 126-127". It displays an optical rotation of 72.5 in chloroform.

Example 4 The acylation of 17ot-ethynyl 19 norandrost 4 ene- 3/3,17fl-diol with 141.5 parts of propionic anhydride, utiizing the processes described in Example 3, affords 17w ethynyl-19-norandrost-4-ene 3,8,17,8-diol 3,17-dipropionate.

Example 5 A solution of 14 parts of 17a-ethynyl-19-norandr0st-4- ens-3,8,17fi-diol and 50 parts of acetic anhydride in 140 parts of pyridine is stored at room temperature, in a nitrogen atmosphere, for about 16 hours, then is carefully poured into cold water. This aqueous mixture is stirred for about minutes, then is filtered to remove the precipitate which has formed. The filter cake is washed successively with warm Water, 10% aqueous hydrochloric acid, and 5% aqueous sodium bicarbonate, then is extracted into ether. The organic layer is separated, dried over anhydrous potassium carbonate containing decolorizing carbon, then stripped of solvent at reduced pressure to afford, as a white solid, 17a-etl1ynyl-19-norandrost-4-ene- 3fi,l7fi-'diol 3-acetate, melting at about 155.5156. It displays an optical rotation of 69 in chloroform.

Example 6 When the procedure of Example 5 is conducted utilizing 63.7 parts of propionic anhydride rather than acetic anhydride, 17a-ethynyl-19-norandrost-4-ene-3fi,17fl-diol 3- propionate is obtained.

Example 7 A solution of one part of 17a-ethyuyl-19-norandrost-4- ene-3/5,17,8-diol 3,17-diacetate in 22 parts by volume of a 0.7 N solution of perbenzoic acid in benzene is stored at about 33 for about 16 hours, then is allowed to Warm to room temperature and is washed successively with dilute aqueous sodium carbonate and water. This benzene solution is then dried over anhydrous sodium sulfate, and the solvent is removed by distillation at reduced pressure. The residual oil solidifies on standing, and the resulting solid is recrystallized from aqueous methanol to afford 4a,5a-epoxy-17a-ethynyl-19 norandrostane 33,175 diol This substance is characterized further by an optical rotation of 38.5 in chloroform and also by the structural formula 0000a, i -czon n T i E 01130 0- 1 O, Example 8 To a solution of 4 parts of 4u,5a-epoxy-17a ethynyl-19- norandrostane-3B,l'Zfl-diol 3,17-di'acetate in 40 parts of methanol is added a solution of 2. parts of sodium carbonate in 20 parts of Water, and this reaction mixture is heated at 50 for about 15 minutes, then is cooled and kept at 0-5 for about 16 hours. The solution is then poured into water, and the precipitate which forms is collected by filtration, washed on the filter with water, and recrystallized from aqueous methanol to afford 40,5aepoxy-lh-ethynyl-19-n0randrostane-3B,17,8-diol 17 acetate. It displays infrared absorption maxima at about 2.75, 3.1, 3.4, 5.78, and 7.92 microns and is represented by the structural formula A solution of 4.7 parts of 17a-et l1ynyl-19-norandrost-4- ene-3B,17,B-diol 3-acetate in parts by volume of a 1.26 N solution of perbenzoic acid in benzene is kept at room temperature for about 2 hours, then at 05 for about 16 hours. This reaction mixture is then washed successively with 5% aqueous sodium bicarbonate and 10% aqueous sodium carbonate until free of oxidant. Several washings with water followed by drying over anhydrous sodium sulfate and removal of the solvent by distillation at reduced pressure affords a glassy residue. This residue is recrystallized from acetone-hexane to afford white platelets of 4u,5a-epoxy-17a-ethynyl-l9=norandrostane 35,175 diol S-acetate, melting at about 176-178. It is represented by the structural formula Example 10 To a solution of 5 parts of 4a.,5a-epoxy-17a-ethynyl-19- norandrostane-B/S',17,8-diol 3-acetate in parts of methanol is added a solution of 1.25 parts of potassium carbonate in 30 parts of water, and this reaction mixture is heated to about 50, then allowed to stand at room temperature for about 30 minutes and finally at 0-5 for about 2 hours. The cooled solution is poured into approx- Example 11 A solution of 7 parts of 17a-ethynyl-l9-norandrost-4- ene-3/8,17/3-diol in 130 parts by volume of a 1.1 N solution of perbenzoic acid in benzene is kept at 0-5 for about 3 hours, then is stored at room temperature for about 2 hours, This reaction mixture is washed successively with aqueous sodium carbonate and water, then is dried over anhydrous sodium sulfate containing decolorizing carbon. Removal of the solvent by distillation at reduced pressure affords a foamy glass-like residue which is crystallized from aqueous methanol to afford 4fi,5,B-epoxy-17a-ethynyl-19-norandrostane 36,17/3 diol hemihydrate, melting at about 142-145". This substance is characterized further by the structural formula Example 12 A mixture of one part of 4B,5B-epoxy-17a-ethynyl-19- norandrostane-3B,17/3-dio1, 3.5 parts of acetic anhydride, and 7 parts of pyridine is stored at room temperature for about 16 hours, then is poured slowly into ice-cold water. The resulting semi-solid precipitate is separated by decantation, then is extracted into ether. The organic layer is separated and washed several times with water, then is dried over anhydrous sodium sulfate containing decolorizing carbon and is concentrated at reduced pressure to afford an oily residue. Crystallization of this residue from acetone-hexane results in pure 45,55-epoxy-17aethynyl-19-norandr0stane-3/3,17fl-diol 3-acetate, melting at about 140-145. It displays an optical rotation of --79 in chloroform and is characterized further by the structural formula O OH iilO 6 Example 13 A solution of 7.5 parts of 17a-ethynyl-19-norandrost-4- ene-3,8,17/3-diol 17-acetate in parts by volume of a 1.1 N solution of perbenzoic acid in benzene is stored at O-5 for about 16 hours, then is washed successively with 10% aqueous sodium carbonate and Water. Drying over anhydrous sodium sulfate followed by distillation of the solvent at reduced pressure affords 45,5,8-epoxy-17a-ethynyl- 19-norandrostane-3fi,l7fl-diol 17-acetate as an oil. This compound can be represented by the structural formula OCOCH Example 14 A mixture of one part of 4fi,5 3-ep0xy-17a-ethynyl-19- norandrostane-3/i,17fl-diol l7-acetate, 3.5 parts of acetic anhydride, and 7 parts of pyridine is allowed to stand at room temperature for about 16 hours, then is poured slowly into ice-cold Water. The semi-solid precipitate which forms is extracted into ether, and the organic extract is washed several times With water, then is dried over anhydrous sodium sulfate containing decolorizing carbon. The solution is stripped of solvent at reduced pressure and the glass-like residue is recrystallized from aqueous methanol to afford 46,5,8-epoxy-17a-ethynl-19-norandrostane-3fi,l7fl-diol 3,17-diacetate. This substance displays infrared absorption peaks at about 3.1, 3.4, 5.78, 7.9, and 9.8 microns. It can be represented by the structural formula CHa OC 0 CH3 O CH 'ilO Example 15 By substituting 1.07 parts of l7a-ethynyl-19-norandrost-4-ene-3a,17a-diol 3,17-dipropionate and otherwise proceeding according to the processes described in Ex ample 7, 4a,5a-epoxy-17a-ethynyl-19-norandrostane-3,B, 17B-diol 3,17-dipropionate is obtained.

Example 16 When 4.28 parts of 4a,Sa-epoxy-17a-ethynyl-19-n0r21ndrostane-3B,17B-diol 3,17-dipropionate is substituted for 4a,5a-epoxy-17a-ethyny1l9-norandrostane 35,175 diol 3,17-diacetate in the procedure of Example 8, 4a,5aepoxy17a-ethynyl-19-norandrostane-3fi, 17B-diol l7-propionate is produced.

Example 18 The reaction of 4.46 parts of propionic anhydride with 45,5,8-epoxy-l7a-ethynyl-19-norandrostane-3fl,17fi-diol by the processes described in Example 12 results in 413,55- epoxy-l7u-ethynyl-l9-norandrostane-3/3,17/5 diol 3-pro pionate.

Example 19 By reacting 7.8 parts of 17u-ethynyl-19-norandrost-4- -ene-3{3,17fl-diol 17-propionate with the perbenzoic acid according to the procedure of Example 13, 45,5B-epoxy- 17rx-ethynyl-l9-norandrostane-3fi,17B-diol l7-propionate is obtained.

Example 20 A mixture of one part of 4fi,5B-epoxy-17a-etl1ynyl-19- norandrostane-3fijl7,8-diol 17-proprionate, 4.4 parts of propionic anhydride, and 9 parts of pyridine is kept at room temperature for about 16 hours. ture is then diluted carefully with cold water, and the resulting aqueous mixture is extracted with ether. The ether solution is washed with water until neutral, then is dried over anhydrous sodium sulfate containing decolorizing carbon. Distillation of the solvent at reduced pressure results in 4B,.55-epoxy-lh-ethynyl-19-norandrostane-3fi,17,B-diol 3,17-dipropionate.

Example 21 The epoxidation of 8.3 parts of 17e-(1-hexynyD-l9-norandrost-4-ene-3e,17fl diol by the processes described in Example 11 results in 45,5;3-epoxy-17a-(1-hexynyl)-l9- norandrostane-3, l7B-diol, represented by the structural formula Example 22 A mixture of 35.6 parts of 17u-(1-l1exynyl)-19-norandrost-4-ene-3,8,17,8-diol, 111 parts of acetic anhydride, and 360 parts of pyridine is stirred and heated at the reflux temperature in a nitrogen atmosphere for about 5 hours. The reaction mixture is cooled and diluted with cold water, and this aqueous mixture is then stirred at room temperature for about one hour. The resulting precipitate is separated by filtration, washed on the filter with water, and dried in air. Extraction of this solid material into ether alfords a solution which is then washed successively with dilute hydrochloride acid and dilute aqueous sodium bicarbonate. The washed solution is dried over anhydrous sodium sulfate, and the solvent is removed by distillation at reduced pressure to aif'ord l7a(1-hexynyl)-l9-norandrost-4-ene-3fl,17 8 diol 3,17-diacetate.

The reaction of 1.15 parts of =17a-(1-hexynyl)-l9-norandros't-4-ene-3fi,17fi-diol, 3,17-diacetate with perbenzoic acid according to the procedure disclosed in Example 7 results in 401,5 epoxy-170M l-hexynyl)-19-norandrostane- 3,8,17B-diol 3,17-diacetate of the structural formula '---c5oornornornom This reaction mix- I Example 23 To a solution of 4.5 parts of 4zx,5u-epoxy-17u-ethynyl- 19-n0randrostane-3B,l7y8-diol B-acetate in 350 parts of pyridine is added 0.5 part of 5% palladium-'on-carbon catalyst, and this reaction mixture is stirred in a hydrogen atmosphere at room temperature and atmospheric pressure until one molecular equivalent of hydrogen is absorbed. The catalyst is removed -by filtration, and the filtrate is concentrated to about /2 volume by distillation at reduced pressure, then is diluted with cold water and cooled at 0-5". The resulting crystals are collected by filtration, dried, and recrystallized from aqueous methanol to afford 4a,5a-epoxy-'17a-vinyl 19 norandrostane-Ilfl,17B-diol 3- acetate, melting at about 141-142. Infrared absorption maxima are observed at about 2.75, 3.4, 5.78, 6.02, and 7.92 microns. This compound can be represented by the structural formula Example 24 A mixture of 5 parts of 4fl,5,8-epoxy-17a-ethynyl-19- norandrostaneddl7B-diol, 0.5 part of 5% palladium-oncarbon catalyst, and 350 parts of pyridine is shaken with hydrogen at atmospheric pressure and room temperature until the absorption of one molecular equivalent of hydrogen is completed. Removal of the catalyst by filtration affords a filtrate which is partially concentrated, then diluted with Water and cooled. The resulting precipitate is collected by filtration, then recrystallized from aqueous methanol, resulting in 4,8,5fl-epoxy-17ot-vinyl-19-norandrostane-3fi,17fi-diol. This substance is characterized further by infrared absorption maxima at about 2.75, 3.4, and 6.02 microns and by the structural formula Example A mixture of 5 parts of 4a,5or-epoxy-17x-ethynyl-19- norandrostane-llfi,l7 8-diol 3-acetate, 0.5 part of 5% palladium-on-carbon catalyst, and 400 parts of ethanol is shaken with hydrogen at atmospheric pressure and room temperature until the uptake of gas ceases. The reaction mixture is filtered through diatomaceous earth, and the filtrate is stripped of solvent by distillation at reduced pressure. The residual oil is crystallized from an aqueous methanol solution to afford 4a,5a-epoxy-17a-ethyl49-norandrostane-BQUB-diol 3-acetate, melting at about 171- 174". It displays infrared absorption maxirna at about 2.75, 3.4, 5.78, and 7.9 microns and is characterized also by the structural formula -ornorr Example 26 To a solution of parts of 4fi,5;8-epoxy-17-u-ethynyl19- norandrostane-3B,17B-diol in 400 parts of ethanol is added 0.5 part of 5% palladium-on-carbon catalyst, and this mixture is shaken with hydrogen at atmospheric pressure and room temperature until hydrogen is no longer absorbed. Removal of the catalyst by filtration through diatornaceous earth affords a solution which is concentrated under reduced pressure, resulting in a semi-solid residue. Crystallization of that residue from aqueous methanol affords '4B,5[3-epoxy-17a-ethyl-19-norandrostane- 33,17B-diol, melting at about 155l58. It is further characterized by infrared absorption maxima at about 2.75 and 3.4 microns and also by the structural formula O Example 27 Example 28 To a solution of 5 parts of 4a,5a-epoxy-17a-rnethyl-19- norandrostane-3,B,l7fi-diol 3-ac'etate in 120 parts of methanol is added a solution of 1.25 parts of potassium carbonate in 30 parts of water, and this reaction mixture is warmed at about 50 for a few minutes, then is cooled to room temperature and allowed to stand for about '30 minutes. Water is added, and the diluted mixture is cooled at 0-5 for about 2 hours, then diluted further with water. The resulting precipitate is collected by filtration, washed on the filter with water, and dried in air. Recrystallization from aqueous acetone, affords 4a,5a-epoxy- 17a-methyl 19 norandrostane-3B,17B-diol, characterized by infrared absorption peaks at about 2.75 and 3.4 microns.

Example 29 The reduction of 5.7 parts of 404,50c-E1J0XY-17oe-(1- hexynyl) l9-norandrostane-3B,17,8-diol =3,l7-diacetate by the procedure described in Example 23 results in 4a,5aepoxy-17a-(l-hexenyl)-l9-norandrostane 3,8,175 diol 3,17-diacetate.

Example 30 When 5.9 parts of 4 3,5[3-epoxy-17a-'( l-hexynyl)-19-norandrostane-3;8,17B-diol is hydrogenated by the processes described in Example 24, 4,6,5fi-epoXy-17oc-(l-hexynyl)- 19-norandrostane-3B,17B-diol is produced.

Example 31 By substiuting 6.37 parts of 4a,5a-epoxy-17a-(lhexynyl) -19-norandrostane-3fl,l7B-diol, 3,17-diacetate and 10 otherwise proceeding according to the processes described in Example 25, 4a,5 a-epoxy-17a-(l-n-hexyl)-19-norandrostane-3;3,l7;3-diol is produced.

Example 32 The substitution of 5.9 parts of 4,8,5/3-epoxy-17a-(lhexynyl)-l9-norandrostane-3fi,1719-diol in the procedure described in Example 26 results in 413,55-epoxy-lh-(l-nhexyl) -19-norandrostane-3/8,17 8-diol.

Example 33 The hydrogenation of 5.03 parts of 4a.,5u-6p0Xy-17aethynyl-19-norandrostane-3B,l7/8-diol 3,17-diacetate in the procedure of Example 23 results in 4a,5a-epoxy-17avinyl-19-norandrostane-3fi,17 3-dio1 3,17-diacctate.

Example 34 By substituting 5.6 parts of 4a,5a-epoxy-17a-ethylnyll9-norandrostane-3/3,17;3-diol 3,17-diacetate and otherwise proceeding according to the processes described in Example 25, 4a,5a-epoxy-17a-ethyl-l9-norandrostane-3fi, 17B-diol 3,17-diaceta-te is obtained.

Example 35 When 5 parts of 4a,5a-epoxy-17a-vinyl-19-norandrostane-3fi,l7 3-diol 3-acetate is hydrolyzed according to the procedure described in Example 10', 4a.,5a-epoxy-17avinyl-19-norandrostane-3B,17B-diol is produced.

Example 36 The hydrolysis of 5 parts of 4a,5a-epoxy-17a-ethyl-19- norandrostane-3;8,17,8-diol 3-acetate by the processes described in Example 10 results in 4a,5a-epoxy-17a-ethyl- 19-norandrostane-3fl,17/3-diol.

Example 37 A solution of 5 parts of 17a-methyl-19-norandrost-4- ene-3(3,17[i-diol in parts by volume of a 1.26 N perbenzoic acid solution in benzene is kept at about 3 for about 16 hours, then is washed successively with water and 10% aqueous sodium carbonate until the excess oxidant is removed. At this point, the organic solution is washed again with water, then is dried over anhydrous sodium sulfate and is stripped of solvent at reduced pressure. Recrystallization of the residue from aqueous acetone affords 45,55 epoxy 17a methyl 19 norandrostane-3,8,17B-diol, which is characterized by infrared absorption peaks at about 2.75 and 3.4 microns.

Example 38 A mixture of one part of 4 8,5fl-epoxy-17a-methyl-l9- norandrostane-3fi,17B-diol, 3.5 parts of acetic anhydride and 7 parts of pyridine is allowed to stand at room temperature for about 16 hours, then is poured carefully into a mixture of ice and water. This aqueous mixture is extracted with ether, and the ether solution is washed successively with dilute hydrochloric acid and water, then is dried over anhydrous sodium sulfate and concentrated to dryness by distillation of the solvent at reduced pressure. The residue is crystallized from aqueous acetone to produce 413,513 epoxy 17oz methyl 19 norandrostane- 3,6,17,3-di0l B-acetate, characterized by infrared absorp tion maxima at about 2.75, 3.4, 5.78, and] 7.92 microns.

What is claimed is:

1. A compound of the formula wherein X represents a. lower aliphatic hydrocarbon radical, and R and R are selected from the group consisting of hydrogen and lower alkanoyl radicals.

2. 4vz,5u-epoxy-17u-vinyl-19-norandrostane-3,8,l7,8-diol 3-acetate.

3. 4a,5u-epoxy-17a-ethyl-19-norandrostane-3fl,.17 8diol B-acetate;

4. A compound of the formula 8. 40,5oc epoxy 17oz --e-thynyl 19 norarldrostane- 3/3,17B-diol 3,17-diacetate.

9. .A compound of the formula i (lower alkynyl) u i (lower elkyl) C O i' (lower alkynyl) 12. A compound of the formula OI-I f (lower alkeny 13. 45,55 epoxy 17a vinyl 19 norandro'stane 35,17/3-diol.

14. A compound of the formula OH p I --(lowcr alkyl) Julian et al. May 5, 1959 Bible et a1. Oct. 13, 1959 UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Patent No 3 ,176 ,015 March 30, 1965 Paul D. Klimstra that error appears in the above numbered pat- It is hereby certified d that the said Letters Patent should read as ent requiring correction an corrected below.

Column 4, line 42,

for "4. 7 read 4 75 column 5, lines 36 to 46, for that portion of the formula re ading l/ZHO read l/ZH O column 6, line 35, for "-ethyn1-" read ethynyl line 54, for "3o,l7q" read -3B,l7B column 7, line 28, for "-3 ,l7B read 3B,l76 column 9, line 70 for "-(l-hexynyl) read (l-hexenyl) column 11, lines 9 to 19, for that portion of the formula reading --(lower alkynyl) H (lower alkynyl) read Signed and sealed this 26th day of October 1965.

(SEAL) fittest:

EDWARD J. BRENNER ERNEST if. SWIDER Commissioner of Patents Attesting Officer 

1. A COMPOUND OF THE FORMULA 